Cigarette smoking is usually initiated in adolescence and constitutes a major cause of disease and premature death. Several pharmacological and behavioral interventions have been used to treat nicotine dependence in adults, but research on the application of these strategies to adolescent nicotine dependence is sparse and has produced mixed results. Promising alternative treatments remain underexplored. The propensity of adolescents for risk-taking and their underdeveloped capacity for self-regulation are two factors thought to contribute to adolescent smoking. These behavioral characteristics likely reflect the maturational delay of prefrontal cortical systems that regulate sub cortical reward circuits. It is therefore important to explore treatment strategies that enhance self-regulation behavior in this age group in efforts to reduce smoking-related morbidity and mortality. Identification of such strategies could also advance understanding of the neural substrates of self-regulation and its development during adolescence. Preliminary studies show that training in yoga-based controlled breathing techniques can reduce smoking and nicotine withdrawal symptoms. However, it is not known whether these effects are linked to enhanced self-regulation. If controlled breathing improves self-regulation, it could have significant potental as a new treatment possibility for adolescent smoking cessation. It is inexpensive, simple to adopt, lacks unpleasant or untoward effects, and does not require extensive training. We propose to investigate the effects of controlled breathing on behavioral indices and neural markers of self-regulation in high-school students who are daily smokers. Participants (ages 14-18) will be trained in controlled breathing techniques. Functional MRI will be used to measure brain activation while participants perform tasks designed to elicit emotional responses, craving, and self-regulation after 30 minutes of controlled breathing as compared to engaging in guided relaxation (control), counterbalanced for order. Brain activation and functional connectivity in structures related to emotion and self-regulation (e.g., amygdala, ventrolateral prefrontal cortex) will be examined. The proposed study will be the first to investigate the effects of a simple, clinically accessible, non- pharmacological technique on behavioral and neural substrates of self-regulation. Positive findings showing that controlled breathing improves self-regulation in the sample tested would justify assessment of this technique as an intervention to reduce adolescent smoking, with potential utility for other applications involving difficulty in regulatin destructive behaviors. ! PUBLIC HEALTH RELEVANCE: Pharmacological and behavioral treatments for adolescent smoking have had modest success while alternative, non-pharmacological treatments remain underexplored. This project will evaluate the behavioral and brain effects of yoga-based controlled breathing on self-regulation abilities of adolescent smokers. The results will potentially inform novel, successful treatment strategies for reducing teen smoking. !